Sulfur-substituted mevinic acid derivatives

Abstract

Antihypercholesterolemic activity is exhibited by compounds of the formula ##STR1## wherein: X is hydrogen, alkali metal or ammonium; Y is hydrogen, alkyl, cycloalkyl, aryl, or aralkyl; ##STR2## R is hydrogen, alkyl, ammonium, alkylammonium, or alkali metal (such as Na, Li, or K); and n is 1 or 2.

What is claimed is: 
     
       1. A compound of the formula ##STR17## wherein: X is hydrogen, alkali metal or ammonium; Y is hydrogen, alkyl, cycloalkyl, aryl, or aralkyl; ##STR18## R is hydrogen, alkyl, ammonium, alkyl-ammonium, or alkali metal; n is 1 or 2 and wherein:     "alkyl" refers to straight and branched chain hydrocarbon groups of 1 to 12 carbon atoms that may be substituted with halo, hydroxy, thio, thio-alkyl, aryl, alkyl-aryl, haloaryl, cycloalkyl, or alkylcycloalkyl groups;   "aryl" and "ar" refer to monocyclic and bicyclic aromatic groups containing from 6 to 10 carbon atoms in the ring, which may be substituted with 1 or 2 lower alkyl groups, 1 to 5 halogen atoms, or 1 or 2 lower alkoxy groups; and   "cycloalkyl" refers to saturated cyclic hydrocarbon groups containing 3 to 12 carbon atoms and may be substituted with 1 or 2 halogens, 1 or 2 lower alkyl groups, or 1 or 2 lower alkoxy groups.   
     
     
       2. The compound of claim 1, wherein X is hydrogen or lithium. 
     
     
       3. The compound of claim 1, wherein Y is hydrogen or alkyl. 
     
     
       4. The compound of claim 1, wherein Y is methyl. 
     
     
       5. The compound of claim 1, wherein Z is ##STR19## 
     
     
       6. The compound of claim 1, wherein Z is ##STR20## and R is lithium. 
     
     
       7. The compound of claim 1 selected from the group consisting of: [1S-[1α(βS*,ΔS*),2α,4aβ,6β,8β,8a.alpha.]]-8-(2,2-Dimethyl-1-oxobutoxy)decahydro-β,Δ-dihydroxy-2-methyl-6-sulfo-1-naphthaleneheptanoic acid, methyl ester; and   [1S-[1α(βS*,ΔS*),2α4aβ,6β,8β,8a.alpha.]]-8-(2,2-Dimethyl-1-oxobutoxy)decahydro-β,Δ-dihydroxy-2-methyl-6-sulfo-1-naphthaleneheptanoic acid, dilithium salt.   
     
     
       8. A hypocholesterolemic or hypolipidemic composition comprising a compound as defined in claim 1 and a pharmaceutically acceptable carrier therefor. 
     
     
       9. A combination comprising a compound as defined in claim 1 and an antihyperlipoproteinemic agent. 
     
     
       10. The combination as defined in claim 9 wherein the antihyperlipoproteinemic agent is probucol, gemfibrozil, a bile acid sequestrant, clofibrate, nicotinic acid, neomycin, p-aminosalicyclic acid or benzafibrate.